We seek to design an orally effective iron-chelating drug for use in patients with beta-thalassemia major. Potential drugs are evaluated both in vitro and in vivo using cultured Chang cells and hypertransfused rats respectively. 2,3-Dihydroxybenzoic acid was identified as being of potential use and has subsequently undergone extensive clinical evaluation. A variety of dihydroxybenzoic acid derivatives have been evaluated but none has proved to be more efficacious than the 2,3-analogue. Accordingly, we are now evaluating multidentate chelating agents which incorporate this moiety. We have also identified several different types of hydroxamic adids. One, rhodotorulic acid, is superior to desferrioxamine, compound must be given parenterally. Tests are now underway to determine its effectiveness as a repository preparation. Cholylhydroxamic acid is orally effective. Presumably this compound behaves as a bile acid analogue entering the enterohepatic circulation and removing iron via the bile. The toxicology of this compound is now being studied. Multidentate bile acid derivatives are also being synthesized as are tropolones and metacyclophanes. In addition, we are studying the role of hydroxamic acids in the spread of bacterial infections as well as the physiological significance of their facile oxidation.